Disclosed are peptide and peptidomimetic compounds generally according to formula (I) that are useful as GHRP analogs:

R.sup.1-A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-R.sup.2   (I)

wherein: A.sup.1 is Aib, Apc or Inp; A.sup.2 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A.sup.3 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A.sup.4 is 2Fua, Orn, 2Pal, 3Pal, 4Pal, Pff, Phe, Pim, Taz, 2Thi, 3Thi, Thr(Bzl); A.sup.5 is Apc, Dab, Dap, Lys, Orn, or deleted; R.sup.1 is hydrogen, (C1-6)alkyl, (C5-14)aryl, (C1-6)alkyl(C5-14)aryl, (C3-8)cycloakyl, or (C2-10)acyl; and R.sup.2 is OH or NH.sub.2;
and pharmaceutical compositions and methods of use thereof.

IAP binding molecules and compositions including these are disclosed. The IAP binding molecules interact with IAPs (inhibitor of apoptosis proteins) in cells and may be used to modify apoptosis in cells treated with such molecules. Embodiments of these compounds have a K.sub.d of less than 0.1 micromolar. Methods of using these IAP binding molecules for therapeutic, diagnostic, and assay purposed are also disclosed.

Various Bcl-2 protein inhibitors are described, along with methods of using them to treat conditions characterized by excessive cellular proliferation, such as cancer and tumors. In various embodiments the Bcl-2 protein inhibitors are compounds or pharmaceutically acceptable salts of the following Formula (I), where the variables in Formula (I) are defined herein. (I)

##STR00001##

Compounds having the general structure A-L-B are presented wherein A and B are independently an E3 ubiquitin ligase protein binding ligand compound of formula 1A or 1B. Pharmaceutical compositions comprising these compounds and methods of use are also presented.

Preparations comprising an enriched population of extracellular vesicles (nEVs) having a negatively charged surface, and that are CD81+ and CD9−, are provided. Improved processes and methods for producing an enriched population of nEVs from non-murine cells, especially human origin cells and/or tissues, are disclosed. Therapeutic methods for using the preparations, including for reducing brain inflammation and treatment of various pathologies associated with brain inflammation, such as by intravenous or intranasal administration, are also described. Methods and preparations for reducing brain inflammation associated with traumatic brain injury (TBI) are also disclosed. A method for treating a patient having suffered a mild traumatic injury (mTMI), or concussion, such as a sports-related head injury, is also disclosed. The nEVs are also demonstrated to reduce the expression level of IL-Iβ in brain tissue of an animal having had traumatic brain injury. Methods for improving cognitive function and performance in animals after a traumatic brain injury is also demonstrated using the preparations of nEVs disclosed herein.

In certain aspects, compounds and uses thereof are provided. In certain aspects, compound-conjugates and uses thereof are provided.

Provided herein are deuterated compounds and compositions useful in increasing PPARδ activity. The compounds and compositions provided herein are useful for the treatment of PPARδ related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

The present invention relates to a compound for stabilizing enzymes, the use of said compound for stabilizing an enzyme, a composition comprising said compound, a method of preparing the composition comprising said compound, a detergent composition comprising said compound and a method of preparing said compound.

A compound of formula (I):

##STR00001##

or pharmaceutically acceptable enantiomer, salt or solvate thereof, or a mixture thereof, the ring A, and the substituents Z, Y and R.sub.1 being as defined herein.

There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, and to their utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for their preparation thereof, and use in medicine. There is particularly provided novel small molecule E3 ubiquitin ligase protein binding inhibitor compounds based on a fluorohydroxyproline scaffold, to their utility as ligands in synthesizing novel PROTACs, and to synthetic methods therefor.